Phagocytosis has essential functions in immunity. Here we highlight the presence of a subcellular level of self–non-self discrimination in dendritic cells that operates at the level of individual phagosomes. We discuss how engagement of Toll-like receptor signaling controls distinct programs of phagosome maturation. An inducible mode of phagosome maturation triggered by these receptors ensures the selection of microbial antigens for presentation by major histocompatibility class II molecules during the simultaneous phagocytosis of self and non-self.